Abstract
Human erythrocytes are indispensable for Plasmodium falciparum development. Unlike other eukaryotic cells, there is no existing erythroid cell line capable of supporting long-term P. falciparum in vitro experiments. Consequently, invasion phenotyping experiments rely on erythrocytes of different individuals. However, the contribution of the erythrocytes variation in influencing invasion rates remains unknown, which represents a challenge for conducting large-scale comparative studies. Here, we used erythrocytes of different blood groups harboring different hemoglobin genotypes to assess the relative contribution of blood donor variability in P. falciparum invasion phenotyping assays. For each donor, we investigated the relationship between parasite invasion phenotypes and erythrocyte phenotypic characteristics, including the expression levels of surface receptors (e.g. the human glycophorins A and C, the complement receptor 1 and decay accelerating factor), blood groups (e.g. ABO/Rh system), and hemoglobin genotypes (e.g. AA, AS and AC). Across all donors, there were significant differences in invasion efficiency following treatment with either neuraminidase, trypsin or chymotrypsin relative to the control erythrocytes. Primarily, we showed that the levels of key erythrocyte surface receptors and their sensitivity to enzyme treatment significantly differed across donors. However, invasion efficiency did not correlate with susceptibility to enzyme treatment or with the levels of the selected erythrocyte surface receptors. Furthermore, we found no relationship between P. falciparum invasion phenotype and blood group or hemoglobin genotype. Altogether, our findings demonstrate the need to consider erythrocyte donor uniformity and anticipate challenges associated with blood donor variability in early stages of large-scale study design.
Highlights
Human erythrocytes are indispensable for Plasmodium falciparum development
Pioneering reports on the major invasion profiles of P. falciparum clinical isolates across various malaria endemic countries have led to the hypothesis that P. falciparum invasion profiles are driven by the intensity of ongoing transmission in any given area[8,9,10,11,12,13,14,15,16]
Untreated erythrocytes from different donors were used in these primary experiments to assess differences in P. falciparum invasion efficiency
Summary
Human erythrocytes are indispensable for Plasmodium falciparum development. Unlike other eukaryotic cells, there is no existing erythroid cell line capable of supporting long-term P. falciparum in vitro experiments. P. falciparum merozoites have the sole purpose to invade erythrocytes and perpetuate the asexual m ultiplication[3] Given their importance in the parasite’s successful invasion and further multiplication within the host cell, merozoite antigens, and invasion-related antigens represent attractive blood-stage vaccine targets. Pioneering reports on the major invasion profiles of P. falciparum clinical isolates across various malaria endemic countries have led to the hypothesis that P. falciparum invasion profiles are driven by the intensity of ongoing transmission in any given area[8,9,10,11,12,13,14,15,16] This proposition has been challenged by recent findings, which have shown no relationship between endemicity and invasion profile when parasites from countries of varying endemicity were subjected to similar protocols[16]. We present results from investigations aimed at assessing the relative contribution of blood donor variability in P. falciparum invasion phenotyping assays (IPAs)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.